Corticostriatal Transmission Is Selectively Enhanced in Striatonigral Neurons with Postnatal Loss of Tsc1

Cell Rep. 2018 Jun 12;23(11):3197-3208. doi: 10.1016/j.celrep.2018.05.037.


mTORC1 is a central signaling hub that integrates intra- and extracellular signals to regulate a variety of cellular metabolic processes. Mutations in regulators of mTORC1 lead to neurodevelopmental disorders associated with autism, which is characterized by repetitive, inflexible behaviors. These behaviors may result from alterations in striatal circuits that control motor learning and habit formation. However, the consequences of mTORC1 dysregulation on striatal neuron function are largely unknown. To investigate this, we deleted the mTORC1 negative regulator Tsc1 from identified striatonigral and striatopallidal neurons and examined how cell-autonomous upregulation of mTORC1 activity affects their morphology and physiology. We find that loss of Tsc1 increases the excitability of striatonigral, but not striatopallidal, neurons and selectively enhances corticostriatal synaptic transmission. These findings highlight the critical role of mTORC1 in regulating striatal activity in a cell type- and input-specific manner, with implications for striatonigral pathway dysfunction in neuropsychiatric disease.

Keywords: D1; D2; Tsc1; autism spectrum disorder; corticostriatal transmission; excitability; mTOR; striatonigral; striatopallidal; striatum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Corpus Striatum / metabolism*
  • Female
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / metabolism*
  • Signal Transduction
  • Synaptic Transmission
  • Tuberous Sclerosis Complex 1 Protein / genetics
  • Tuberous Sclerosis Complex 1 Protein / metabolism*


  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Mechanistic Target of Rapamycin Complex 1